A central enrichment-based comparison of two alternative methods of generating transcription factor binding motifs from protein binding microarray data

Characterising transcription factor binding sites (TFBS) is an important problem in bioinformatics, since predicting binding sites has many applications such as predicting gene regulation. ChIP-seq is a powerful in vivo method for generating genome-wide putative binding regions for transcription factors (TFs). CentriMo is an algorithm that measures central enrichment of a motif and has previously been used as motif enrichment analysis (MEA) tool. CentriMo uses the fact that ChIP-seq peak calling methods are likely to be biased towards the centre of the putative binding region, at least in cases where there is direct binding. CentriMo calculates a binomial p-value representing central enrichment, based on the central bias of the binding site with the highest likelihood ratio. In cases where binding is indirect or involves cofactors, a more complex distribution of preferred binding sites may occur but, in many cases, a low CentriMo p-value and low width of maximum enrichment (about 100bp) are strong evidence that the motif in question is the true binding motif. Several other MEA tools have been developed, but they do not consider motif central enrichment. The study investigates the claim made by Zhao and Stormo (2011) that they have identified a simpler method than that used to derive the UniPROBE motif database for creating motifs from protein binding microarray (PBM) data, which they call BEEML-PBM (Binding Energy Estimation by Maximum Likelihood-PBM). To accomplish this, CentriMo is employed on 13 motifs from both motif databases. The results indicate that there is no conclusive difference in the quality of motifs from the original PBM and BEEML-PBM approaches. CentriMo provides an understanding of the mechanisms by which TFs bind to DNA. Out of 13 TFs for which ChIP-seq data is used, BEEML-PBM reports five better motifs and twice it has not had any central enrichment when the best PBM motif does. PBM approach finds seven motifs with better central enrichment. On the other hand, across all variations, the number of examples where PBM is better is not high enough to conclude that it is overall the better approach. Some TFs bind directly to DNA, some indirect or in combination with other TFs. Some of the predicted mechanisms are supported by literature evidence. This study further revealed that the binding specificity of a TF is different in different cell types and development stages. A TF is up-regulated in a cell line where it performs its biological function. The discovery of cell line differences, which has not been done before in any CentriMo study, is interesting and provides reasons to study this further

Stability of gold and cerium oxide nanoparticles in aqueous environments, and their effects on Pseudokirchneriella subcapitata and Salvinia minima

Engineered nanoparticles (ENPs) are class of emerging environmental pollutants, generally found at low concentrations and are therefore likely to exert sub-lethal effects on aquatic organisms. Among different kinds of NPs, metal and metal oxides NPs are most widely used in consumer products, targeted drug delivery and optical bioimaging. Rapid increasing use and applications of ENPs and their consequent emission into the environments raised the need to understand their potential effects to ecological systems. Yet, currently, the environmental fate, behaviour and potential toxic effects of NPs in the environment are poorly understood. The aquatic environment is at risk of exposure to NPs, as it acts as a final recipient for most environmental contaminants. To address this knowledge gap, the current study seeks to generate data on the fate and behaviour of NPs in aquatic systems and investigates their potential toxic effects on aquatic organisms. Amongst the less studied, but widely produced NPs are gold and cerium oxide NPs, therefore, likely to be released into the environment in high quantities. Algae, Pseudokirchneriella subcapitata and aquatic higher plant, Salvinia minima were selected as models for this study owing to limited nano-ecotoxicity data available. To investigate the influence of physicochemical properties of NPs and media constituents on the environmental fate and behaviour of NPs; the hydrodynamic diameters and zeta potentials for Au (5, 20 and 40 nm; citrate and branched polyethyleneimine coated) and CeO2 (>25 nm, uncoated) NPs were characterized in de-ionised water (DIW), 10% Hoagland’s medium, dechlorinated tap water and 10% BG-11 algal medium. Findings showed high agglomeration of NPs in biological media compared to DIW due to the low ionic strength of DIW. Instability of NPs in media was size and surface coating dependent, with smaller sized (5 nm) and citrate coated-Au NPs agglomerating rapidly. The much broader particle size distribution observed indicated (i) formation of agglomerates, (ii) instability of Au and CeO2 NPs in ecotoxicological media and (iii) inaccuracy of light scattering techniques in size analysis for non-spherical NPs. The interaction of Au and CeO2 NPs with S. minima indicated that (i) NPs were not internalized by S. minima irrespective of NP size, coating variant, and type, (ii) NPs can be adsorbed on the roots of S. minima but without inducing morphological level effects such as growth retardation and necrosis and (iii) adsorption was established as mechanism of NPs accumulation in S. minima. Exposure of P. subcapitata to NPs showed that (i) citrate-Au and CeO2 NPs neither inhibited P. subcapitata growth nor affected the cellular chlorophyll content; where slight growth inhibition was observed at 72 h, algae recovered after 96 h, (ii) genotoxicity assays revealed potential toxicity of NPs to algae at molecular level although no effects observed at morphological level and (iii) algae show an increase in genomic stability under long-term exposure conditions. Overall, the study showed that the behaviour of NPs in aquatic systems and their interactions with aquatic organisms are influenced by their physicochemical characteristics, exposure medium composition and exposure period; also, genotoxicity assays are more sensitive than cytotoxicity assays.Thesis (PhD)--University of Pretoria, 2019.GeneticsPhDUnrestricte

Cytotoxicity and genotoxicity of coated-gold nanoparticles on freshwater algae Pseudokirchneriella subcapitata

Gold engineered nanoparticles (nAu) are increasingly detected in ecosystems, and this raises the need to establish their potential effects on aquatic organisms. Herein, cytotoxic and genotoxic effects of branched polyethylenimine (BPEI)- and citrate (cit)-coated nAu (5, 20, and 40 nm) on algae Pseudokirchneriella subcapitata were evaluated. The apical biological endpoints: growth inhibition and chlorophyll a (Chl a) content were investigated at 62.5–1000 µg/L over 168 h. In addition, the apurinic/apyrimidinic (AP) sites, randomly amplified polymorphic deoxyribonucleic acid (RAPD) profiles, and genomic template stability (GTS) were assessed to determine the genotoxic effects of nAu. The results show algal growth inhibition at 5 nm BPEI-nAu up to 96 h, and thereafter cell recovery except at the highest concentration of 1000 µg/L. Insignificant growth reduction for cit-nAu (all sizes), as well as 20 and 40 nm BPEI-nAu, was observed over 96 h, but growth promotion was apparent at all exposures thereafter except for 40 nm BPEI-nAu at 250 µg/L. A decrease in Chl a content following exposure to 5 nm BPEI-nAu at 1000 µg/L corresponded to significant algal growth reduction. In genotoxicity studies, a significant increase in AP sites content was observed relative to the control – an indication of nAu ability to induce genotoxic effects irrespective of their size and coating type. For 5 nm- and 20 nm-sized nAu for both coating types and exposure concentrations no differences in AP sites content were observed after 72 and 168 h. However, a significant reduction in AP sites was observed following algae exposure to 40 nm-sized nAu (irrespective of coating type and exposure concentration) at 168 h compared to 72 h. Thus, AP sites results at 40 nm-size suggest likely DNA damage recovery over a longer exposure period. The findings on AP sites content showed a good correlation with an increase in genome template stability and growth promotion observed after 168 h. In addition, RAPD profiles demonstrated that nAu can induce DNA damage and/or DNA mutation to P. subcapitata as evidenced by the appearance and/or disappearance of normal bands compared to the controls. Therefore, genotoxicity results revealed significant toxicity of nAu to algae at the molecular level although no apparent effects were detectable at the morphological level. Overall, findings herein indicate that long-term exposure of P. subcapitata to low concentrations of nAu may cause undesirable sub-lethal ecological effects.The South African National Research Foundation, Department of Science and Technology Professional Development Programme Doctoral grant, the Council for Scientific and Industrial Research (CSIR) and the University of Pretoria.https://www.elsevier.com/locate/aqtox2022-05-24hj2022Chemical Engineerin

Interactions of coated-gold engineered nanoparticles with aquatic higher plant Salvinia minima baker

The study investigated the interactions of coated-gold engineered nanoparticles (nAu) with the aquatic higher plant Salvinia minima Baker in 2,7, and 14 d. Herein, the nAu concentration of 1000 g/L was used; as in lower concentrations, analytical limitations persisted but >1000 g/L were deemed too high and unlikely to be present in the environment. Exposure of S. minima to 1000 g/L of citrate (cit)- and branched polyethyleneimine (BPEI)-coated nAu (5, 20, and 40 nm) in 10% Hoagland’s medium (10 HM) had marginal effect on biomass and growth rate irrespective of nAu size, coating type, or exposure duration. Further, results demonstrated that nAu were adsorbed on the plants’ roots irrespective of their size or coating variant; however, no evidence of internalization was apparent, and this was attributed to high agglomeration of nAu in 10 HM. Hence, adsorption was concluded as the basic mechanism of nAu accumulation by S. minima. Overall, the long-term exposure of S. minima to nAu did not inhibit plant biomass and growth rate but agglomerates on plant roots may block cell wall pores, and, in turn, alter uptake of essential macronutrients in plants, thus potentially affecting the overall ecological function.Supplementary Materials: Equation (S1): Calculation of ζ potentials using Smoluchowski equation, Equation (S2): Calculation of ionic strength (IS) of the exposure medium, Figure S1: TEM images of nAu (a) 5 nm-Cit, (b) 20 nm-Cit, (c) 40 nm-Cit, (d) 5 nm-BPEI, (e) 20 nm-BPEI, (f) and 40 nm-BPEI, Table S1: Composition of Hoagland’s medium, Table S2: Mean sizes (nm) of nAu obtained using TEM, Figure S2: Particle size distribution of nAu at 1000 µg/L in 10% Hoagland’s medium measured using Dynamic Light Scattering technique (a) 5 nm Cit-nAu, (b) 20 nm Cit-nAu, (c) 40 nm Cit-nAu, (d) 5 nm BPEI-nAu, (e) 20 nm BPEI-nAu, and (f) 40 nm BPEI-nAu, Figure S3: Hydrodynamic diameters of nAu in de-ionized water and 10% Hoagland’s medium tracked using Dynamic Light Scattering technique over 48 h; (a) 5 nm Cit-nAu, (b) 20 nm Cit-nAu, (c) 40 nm Cit-nAu, (d) 5 nm BPEI-nAu, (e) 20 nm BPEI-nAu, and (f) 40 nm BPEI-nAu, Figure S4: Zeta potentials of nAu in de-ionized water and 10% Hoagland’s medium obtained using Dynamic Light Scattering technique over 48 h; (a) 5 nm Cit-nAu, (b) 20 nm Cit-nAu, (c) 40 nm Cit-nAu, (d) 5 nm BPEI-nAu, (e) 20 nm BPEI-nAu, and (f) 40 nm BPEI-nAu, Figure S5: UV-vis spectrum of nAu in de-ionized water as a function of time; (a) 5 nm Cit-nAu, (b) 20 nm Cit-nAu, (c) 40 nm Cit-nAu, (d) 5 nm BPEI-nAu, (e) 20 nm BPEI-nAu, and (f) 40 nm BPEI-nAu, Figure S6: in situ nAu concentration (particles/mL) examined using Nanoparticle Tracking Analysis (NTA), Figure S7: TEM-EDX spectra confirming the absence of nAu internalization on plant roots: (a) control, (b) 5 nm cit-nAu, (c) 20 nm-cit nAu, (d) 40 nm cit-nAu, (e) 5 nm BPEI-nAu, (f) 20 nm BPEI-nAu, and (g) 40 nm BPEI.The South African National Research Foundation and Department of Science and Technology Professional Development Programme Doctoral Scholarship, the Council for Scientific and Industrial Research and the University of Pretoria.https://www.mdpi.com/journal/nanomaterialsam2022Chemical Engineerin

Popularising semiotics.

Semiotics, deconstructionism, structuralism and postmodernism are words which lurk on boundaries of the consciousness of most of us. But they remain shadowy presences except on the rare occasions when we need to wrestle out of them an explanation of just what they are all about. In this issue of Trends we grapple with one of them, semiotics. C. S. Peirce, the American, pragmatist philosopher who coined the term, saw semiotics as a 'method of methods', useful in many disciplines to clarify their own theory and practice. Everyone uses signs and symbols. Everyone thinks they know the meanings of the signs and symbols they use. But why do they have meanings? Where do the meanings come from? Why are the signs and symbols used by one person or group so frequently misinterpreted by others? Semiotics may seem esoteric, but its interests are central to all communication. Consequently all communicators should be concerned with at least some of the problems dealt with semioticians. To guide us on our exploration of semiotics the publishers of Trends, the Centre for the Study of Communication and Culture, have enlisted the aid of Professor Keyan Tomaselli and his colleagues at the Centre for Cultural and Media Studies of the University of Natal, who for some years have been studying the cultural side of semiotics. So eager has their response been that we have devoted two issues of Trends to their reports. The contents of these two issues manifest the views of the authors more than is usual for Trends, and they are not necessarily those of the editors; but the CSCC feels that the perspective of the CCMS deserves both expression and discussion

Effects of Two Antiretroviral Drugs on the Crustacean Daphnia magna in River Water

Antiretroviral (ARVs) drugs are used to manage the human immunodeficiency virus (HIV) disease and are increasingly being detected in the aquatic environment. However, little is known about their effects on non-target aquatic organisms. Here, Daphnia magna neonates were exposed to Efavirenz (EFV) and Tenofovir (TFV) ARVs at 62.5–1000 µg/L for 48 h in river water. The endpoints assessed were mortality, immobilization, and biochemical biomarkers (catalase (CAT), glutathione S-transferase (GST), and malondialdehyde (MDA)). No mortality was observed over 48 h. Concentration- and time-dependent immobilization was observed for both ARVs only at 250–1000 µg/L after 48 h, with significant immobilization observed for EFV compared to TFV. Results for biochemical responses demonstrated that both ARVs induced significant changes in CAT and GST activities, and MDA levels, with effects higher for EFV compared to TFV. Biochemical responses were indicative of oxidative stress alterations. Hence, both ARVs could potentially be toxic to D. magna

Interactions of Coated-Gold Engineered Nanoparticles with Aquatic Higher Plant Salvinia minima Baker

The study investigated the interactions of coated-gold engineered nanoparticles (nAu) with the aquatic higher plant Salvinia minima Baker in 2,7, and 14 d. Herein, the nAu concentration of 1000 µg/L was used; as in lower concentrations, analytical limitations persisted but >1000 µg/L were deemed too high and unlikely to be present in the environment. Exposure of S. minima to 1000 µg/L of citrate (cit)- and branched polyethyleneimine (BPEI)-coated nAu (5, 20, and 40 nm) in 10% Hoagland’s medium (10 HM) had marginal effect on biomass and growth rate irrespective of nAu size, coating type, or exposure duration. Further, results demonstrated that nAu were adsorbed on the plants’ roots irrespective of their size or coating variant; however, no evidence of internalization was apparent, and this was attributed to high agglomeration of nAu in 10 HM. Hence, adsorption was concluded as the basic mechanism of nAu accumulation by S. minima. Overall, the long-term exposure of S. minima to nAu did not inhibit plant biomass and growth rate but agglomerates on plant roots may block cell wall pores, and, in turn, alter uptake of essential macronutrients in plants, thus potentially affecting the overall ecological function

Exploring Educators’ Perception on learner’s right affecting discipline in Secondry Schools

The aim of this study was to investigate educator’s perceptions of how learners’ rights to safety affect disciplinary procedures in secondary schools in the Umbumbulu Circuit of KwaZulu-Natal. The paper adopted a qualitative approach, where semi-structured interviews were used to collect data from 10 purposively selected educators. The thematic analysis technique was employed to analyse the data. The main findings of the study indicated that educators had their own perceptions of how learners’ rights to safety affect the way they attend to disciplinary issues when a learner has transgressed. The educators’ perceptions of learners’ rights to safety affect disciplinary procedures for many reasons, including poor understanding of relevant education laws and policies. The results also showed that teachers think that the legislation guiding teaching and learning, as well as disciplinary procedures, are marred with contradictions, which make discipline management not only difficult, but also exposes both the learners and the educators to unsafe environments. The study also indicated that the teachers are sensitive to learners’ rights to safety, resulting in restricted attention to learners who are guilty of an offence in the school. In light of these findings, it was recommended that there should be a mandatory continuous in-service workshop for the educators, on how learner discipline can be maintained

Effects of two antiretroviral drugs on the crustacean Daphnia magna in river water

Antiretroviral (ARVs) drugs are used to manage the human immunodeficiency virus (HIV) disease and are increasingly being detected in the aquatic environment. However, little is known about their effects on non-target aquatic organisms. Here, Daphnia magna neonates were exposed to Efavirenz (EFV) and Tenofovir (TFV) ARVs at 62.5–1000 g/L for 48 h in river water. The endpoints assessed were mortality, immobilization, and biochemical biomarkers (catalase (CAT), glutathione S-transferase (GST), and malondialdehyde (MDA)). No mortality was observed over 48 h. Concentration- and time-dependent immobilization was observed for both ARVs only at 250–1000 g/L after 48 h, with significant immobilization observed for EFV compared to TFV. Results for biochemical responses demonstrated that both ARVs induced significant changes in CAT and GST activities, and MDA levels, with effects higher for EFV compared to TFV. Biochemical responses were indicative of oxidative stress alterations. Hence, both ARVs could potentially be toxic to D. magna.SUPPLEMENTARY MATERIALS : TABLE S1: Classes and types of individual Food and Drug Administration-approved ARVs for clinical use; TABLE S2: Global measured environmental concentrations of ARVs in different matrices [3,22,53,81,82]; TABLE S3: Molecular Formula and physico-chemical properties of ARVs; TABLE S4: Physicochemical parameters of freshwater samples collected from Elands River; TABLE S5: Physicochemical properties of ER water during exposure recorded for the controls, lowest and highest exposure concentrations at 0 and 48 h; TABLE S6: Cumulative immobilization of D. magna exposed to variant concentrations of EFV and TFV.Water Research Commission (WRC) South Africa.https://www.mdpi.com/journal/toxicsam2023Chemical Engineerin

SHEMBE PHILOSOPHY: THE DECOLONISATION OF RELIGION AND SPIRITUALITY

This piece of scholarly work in the sight of the public is crafted to drive or to win any theological debate or argument but I simple seek to advance the understanding of Shembe in the specific area of His philosophy not the holistic Shembe. This I say because no one on earth can claim in totality that he or she has a better understanding of Shembe, hence choosing the concept of philosophy which is the critical examination of ground fundamental beliefs and analysis of concept, doctrines, and practices was relevant. The process of decolonization has been a significant area of scholarly inquiry in various fields, including religion and spirituality. Shembe philosophy placed a strong emphasis on cultural revival and the restoration of African spiritual practices. The movement sought to reclaim African spirituality while accommodating certain aspects of organic Christianity. Central to Shembe philosophy was to reconnect the so-called lost generation of Abantu in the ancestral connection, the veneration of ancestors, and the preservation of African traditions (Wababa, 2018). The complexity of such role from Jehovah was delicate and crucial. Isaiah Shembe known as Umqaliwendlela would hear a voice singing new unexpected words. A qualitative study method was employed in this study to enable a comprehensive exploration of the experiences, perspectives, and practices within Shembe communities. The study findings revealed that the key principles and teachings of Shembe philosophy have now a massive influence and understanding of decolonization in guiding the community’s beliefs and practices. The community have incorporation of Shembe philosophy into their daily lives for decolonial transformation. The findings further revealed although numerous challenges faced by the Shembe community in their pursuit of decolonization and cultural heritage preservation, but the post-colonial era in South Africa has made much better to defend His philosophy using the current constitution chapter 2 which clearly stipulates in the Bill of Rights, which states that everyone has right to freedom of religion, belief, and opinion. Section 9, the equality clause, prohibits unfair discrimination on various grounds including religion. Shembe fought spiritual the above religious right from as early as 1900 until the formation of the South African Native National Congress (SANNC), later known as the African National Congress (ANC) on the 08 January 1912. In conclusion, the Shembe philosophy has lightning influence in guiding the community’s beliefs and practices. The post-colonial role of Shembe philosophy in the decolonization of religion and spirituality requires further exploration and development